BME PhD Prospectus Defense - Jonah A. Kaplan

9:30 am on Monday, April 22, 2013
11:30 am on Monday, April 22, 2013
44 Cummington St, Room 203
Title: “Mechanoresponsive Drug Delivery Depots”

Committee Members:
Prof. Mark W. Grinstaff, Ph.D. (Advisor, Chair)
Prof. Dimitrije Stamenovic, Ph.D. (BME)
Prof. Yolonda L. Colson, MD, Ph.D. (Thoracic Surgery, Brigham and Women’s Hospital)
Prof. Yanhang (Katherine) Zhang, Ph.D. (ME)

Stimuli-responsive materials in the context of drug delivery offer better spatiotemporal control over dose administration—that is, getting the drug or agent to the specific cells/tissues that need it. In general, these stimuli-responsive delivery depots release their drug payload in response to such stimuli as temperature, pH, electrical potential, magnetic field, and ultrasound. Relatively understudied are drug delivery materials that are responsive to applied mechanical deformation. This proposal therefore seeks to develop a relatively new concept in controlled release systems: using mechanical force as a trigger for releasing entrapped drug payloads from within mechanoresponsive networks. Three-dimensional networks provide a unique strategy for constructing mechanoresponsive drug delivery depots, whereby mechanical deformation of the network increases its permeability to water and macromolecules (i.e., immunoglobulins). Therefore, the goal of this work is to develop mechanoresponsive drug delivery materials from 3-dimensional supramolecular and polymeric networks. The first aim will study mechanical shear as a mechanical stimulus for the release of a monoclonal antibody from a self-healing nanofiber low molecular weight hydrogel (LMWH) for treating rheumatoid arthritis. The second aim will focus on tension as a mechanical stimulus for the release of chemotherapy agents from nano- and microfiber polymer meshes fabricated by the electrospinning process. Completion of these aims will result in a detailed understanding of a new design strategy for developing mechanoresponsive materials for drug delivery: using the principles of network organization—and subsequent destabilization—to facilitate the diffusion of entrapped agents out of these networks.